二氢青蒿素杂合体的抗肿瘤活性研究进展

Recent Updates on Anticancer Activity of Dihydroartemisinin Hybrids

化疗药物是治疗肿瘤的重要武器,目前已上市的抗肿瘤化疗药物数以百计。然而,经过一段时间的治疗,肿瘤细胞不可避免地会产生耐药性,且替代方案往往存在毒副作用明显和特异性不高等缺点。因此,开发具有高活性和高特异性的新型抗肿瘤化疗药物仍是目前药物化学家所必须面对的巨大挑战。二氢青蒿素类化合物可通过阻滞肿瘤细胞周期、抑制肿瘤血管生成、诱导DNA损伤和铁死亡等作用机制发挥抗肿瘤活性,对包括耐多药肿瘤在内的多种肿瘤具有良好的体内外活性。其中,二氢青蒿素杂合体具有提高抗肿瘤活性、克服耐药性、降低毒副作用和改善药动学性质的潜力,已成为寻找新型抗肿瘤药物的重要来源。本文将着重介绍2018—2022年所发展的具有体内外抗肿瘤活性的二氢青蒿素杂合体的最新研究进展。

Chemotherapeutics are effective weapons for cancer treatment,and hundreds of drugs have been approved for clinical applications.However,cancer cells inevitably develop drug resistance after a period of treatment,and alternative strategies often suffer from serious side effects and low specificity.Therefore,the development of new anticancer chemotherapeutics with high activity and other desirable therapeutic indicators remains a critically important endeavor.Dihydroartemisinin derivatives could exert diverse anticancer mechanisms,inclusive of cell cycle inhibition,inhibition of tumor angiogenesis,induction of DNA damage,and ferroptosis.Accordingly,derivatives of dihydroartemisinin,including multidrug-resistant malignancies,show promising in vitro and in vivo action against a variety of cancers as a result.Among them,dihydroartemisinin hybrids have the potential to enhance anticancer activity,overcome drug resistance,reduce side effects,and improve pharmacokinetic properties,and have already become an important source for the discovery of new anticancer drugs.This review focuses on the in vitro and in vivo anticancer efficiency of dihydroartemisinin hybrids,along with the structure-activity relationships as well as mechanisms of action,covering articles published in recent five years.